Maksymilian Prondzynski
MSc, PhD
Investigator, BC Children's Hospital
Advanced Materials
Murat Kaynak and Mehmet D. Asik and Elif E. Inan and Maksymilian Prondzynski and Hamzeh Ghasemzadeh and Amir Poorghani and Yashasvi Tharani and Matilda Holtz and Daryush D. Mehta and William T. Pu and Orhun K. Muratoglu and Martin L. Yarmush and Alexander Alexeev and O. Berk Usta
DOI: 10.1002/adma.20250967511 / 2025
Mengmeng Huang and Feria A. Ladha and Yunxia Wang and Michael A. Trembley and Hui-Min Yin and Rongbin Zheng and Maksymilian Prondzynski and Yashavi Tharani and Alexander A. Akerberg and Stefan Aigner and Brian A. Yee and Joshua Mayourin and Sarah U. Morton and Vassilios J. Bezzerides and William T. Pu and Gene W. Yeo and Kaifu Chen and C. Geoffrey Burns and Caroline E. Burns
DOI: 10.1101/2025.10.28.68521410 / 2025
Circulation
Lu, F. and Wu, Z. and Chi, S. and Wang, Y. and Ponek, A. and Ma, Q. and Chen, C. and Shi, B. and Pavlaki, N. and Liou, C. and Tharani, Y. and Prondzynski, M. and Talab, S.S. and Xie, W. and Chen, Y.S. and Guo, Z. and Lipsitz, S.R. and Zhang, D. and van Petegem, F. and Bezzerides, V.J. and Pu, W.T.
DOI: 10.1161/CIRCULATIONAHA.125.075402Research Square
Choudhury, S. and Hilal, N. and An, Z. and Prondzynski, M. and Matsui, E. and Sahu, D. and Mao, S. and Jung, Y.L. and Yang, Y. and Epstein, S. and Chen, M.-H. and Pu, W. and Del Monte, F. and Huang, A.Y.
DOI: 10.21203/rs.3.rs-5875531/v1Nature Biomedical Engineering
Lu, F. and Liou, C. and Ma, Q. and Wu, Z. and Xue, B. and Xia, Y. and Xia, S. and Trembley, M.A. and Ponek, A. and Xie, W. and Shani, K. and Bortolin, R.H. and Prondzynski, M. and Berkson, P. and Zhang, X. and Naya, F.J. and Bedi, K.C. and Margulies, K.B. and Zhang, D. and Parker, K.K. and Pu, W.T.
DOI: 10.1038/s41551-024-01253-zResearch Square
Bezzerides, V. and Yoshinaga, D. and Feng, R. and Prondzynski, M. and Shani, K. and Tharani, Y. and Mayourian, J. and Joseph, M. and Walker, D. and Bortolin, R. and Carreon, C. and Boss, B. and Upton, S. and Parker, K. and Pu, W.
DOI: 10.21203/rs.3.rs-3398860/v1Nature Communications
Prondzynski, M. and Berkson, P. and Trembley, M.A. and Tharani, Y. and Shani, K. and Bortolin, R.H. and Sweat, M.E. and Mayourian, J. and Yucel, D. and Cordoves, A.M. and Gabbin, B. and Hou, C. and Anyanwu, N.J. and Nawar, F. and Cotton, J. and Milosh, J. and Walker, D. and Zhang, Y. and Lu, F. and Liu, X. and Parker, K.K. and Bezzerides, V.J. and Pu, W.T.
DOI: 10.1038/s41467-024-50224-0Circulation
Bortolin, R.H. and Nawar, F. and Park, C. and Trembley, M.A. and Prondzynski, M. and Sweat, M.E. and Wang, P. and Chen, J. and Lu, F. and Liou, C. and Berkson, P. and Keating, E.M. and Yoshinaga, D. and Pavlaki, N. and Samenuk, T. and Cavazzoni, C.B. and Sage, P.T. and Ma, Q. and Whitehill, R.D. and Abrams, D.J. and Carreon, C.K. and Putra, J. and Alexandrescu, S. and Guo, S. and Tsai, W.-C. and Rubart, M. and Kubli, D.A. and Mullick, A.E. and Bezzerides, V.J. and Pu, W.T.
DOI: 10.1161/CIRCULATIONAHA.123.068111Frontiers in Physiology
Prondzynski, M. and Pioner, J.M. and Sala, L. and Bellin, M. and Meraviglia, V.
DOI: 10.3389/fphys.2024.1378495Biorxiv
Prondzynski, M. and Bortolin, R.H. and Berkson, P. and Trembley, M.A. and Shani, K. and Sweat, M.E. and Mayourian, J. and Cordoves, A.M. and Anyanwu, N.J. and Tharani, Y. and Cotton, J. and Milosh, J.B. and Walker, D. and Zhang, Y. and Liu, F. and Liu, X. and Parker, K.K. and Bezzerides, V.J. and Pu, W.T.
DOI: 10.1101/2024.02.24.581789Biorxiv
Douvdevany, G. and Erlich, I. and Haimovich-Caspi, L. and Mashiah, T. and Prondzynski, M. and Pricolo, M.R. and Alegre-Cebollada, J. and Linke, W.A. and Carrier, L. and Kehat, I.
DOI: 10.1101/2023.08.31.555653Circulation
Cao, Y. and Zhang, X. and Akerberg, B.N. and Yuan, H. and Sakamoto, T. and Xiao, F. and Vandusen, N.J. and Zhou, P. and Sweat, M.E. and Wang, Y. and Prondzynski, M. and Chen, J. and Zhang, Y. and Wang, P. and Kelly, D.P. and Pu, W.T.
DOI: 10.1161/CIRCULATIONAHA.122.061955Nature Cardiovascular Research
Sweat, M.E. and Cao, Y. and Zhang, X. and Burnicka-Turek, O. and Perez-Cervantes, C. and Kulandaisamy, A. and Lu, F. and Keating, E.M. and Akerberg, B.N. and Ma, Q. and Wakimoto, H. and Gorham, J.M. and Hill, L.D. and Song, M.K. and Trembley, M.A. and Wang, P. and Gianeselli, M. and Prondzynski, M. and Bortolin, R.H. and Bezzerides, V.J. and Chen, K. and Seidman, J.G. and Seidman, C.E. and Moskowitz, I.P. and Pu, W.T.
DOI: 10.1038/s44161-023-00334-7Nature Cardiovascular Research
Sweat, M.E. and Cao, Y. and Zhang, X. and Burnicka-Turek, O. and Perez-Cervantes, C. and Kulandaisamy, A. and Lu, F. and Keating, E.M. and Akerberg, B.N. and Ma, Q. and Wakimoto, H. and Gorham, J.M. and Hill, L.D. and Song, M.K. and Trembley, M.A. and Wang, P. and Gianeselli, M. and Prondzynski, M. and Bortolin, R.H. and Bezzerides, V.J. and Chen, K. and Seidman, J.G. and Seidman, C.E. and Moskowitz, I.P. and Pu, W.T.
DOI: 10.1038/s44161-023-00373-0EMBO molecular medicine
Prondzynski, M. and Lemoine, M.D. and Zech, A.T. and Horv{\'a}th, A. and Di Mauro, V. and Koivum{\"a}ki, J.T. and Kresin, N. and Busch, J. and Krause, T. and Kr{\"a}mer, E. and Schlossarek, S. and Spohn, M. and Friedrich, F.W. and M{\"u}nch, J. and Laufer, S.D. and Redwood, C. and Volk, A.E. and Hansen, A. and Mearini, G. and Catalucci, D. and Meyer, C. and Christ, T. and Patten, M. and Eschenhagen, T. and Carrier, L.
DOI: 10.15252/emmm.202216423Cells
Zech, A.T.L. and Prondzynski, M. and Singh, S.R. and Pietsch, N. and Orthey, E. and Alizoti, E. and Busch, J. and Madsen, A. and Behrens, C.S. and Meyer-Jens, M. and Mearini, G. and Lemoine, M.D. and Kr{\"a}mer, E. and Mosqueira, D. and Virdi, S. and Indenbirken, D. and Depke, M. and Salazar, M.G. and V{\"o}lker, U. and Braren, I. and Pu, W.T. and Eschenhagen, T. and Hammer, E. and Schlossarek, S. and Carrier, L.
DOI: 10.3390/cells11172745Advanced Materials
Kumar, R. and Mancebo, J.G. and Patenaude, R. and Sack, K. and Prondzynski, M. and Packard, A.B. and Dearling, J.L.J. and Li, R. and Balcarcel-Monzon, M. and Dominguez, S. and Emani, S. and Kheir, J.N. and Polizzotti, B. and Peng, Y.
DOI: 10.1002/adma.202207376Circulation
DOI: 10.1161/circulationaha.120.048698 PubMed: 3379330304 / 2021
Cardiovascular Research
Marta Lemme and Ingke Braren and Maksymilian Prondzynski and Blent Aksehirlioglu and Brbel M Ulmer and Mirja L Schulze and Djemail Ismaili and Christian Meyer and Arne Hansen and Torsten Christ and Marc D Lemoine and Thomas Eschenhagen
DOI: 10.1093/cvr/cvz24507 / 2020
Cardiovascular Research
Vassilios J Bezzerides and Maksymilian Prondzynski and Lucie Carrier and William T Pu
DOI: 10.1093/cvr/cvaa10707 / 2020
Cells
Andrs Horvth and Torsten Christ and Jussi T. Koivumki and Maksymilian Prondzynski and Antonia T. L. Zech and Michael Spohn and Umber Saleem and Ingra Mannhardt and Brbel Ulmer and Evaldas Girdauskas and Christian Meyer and Arne Hansen and Thomas Eschenhagen and Marc D. Lemoine
DOI: 10.3390/cells901025301 / 2020
EMBO Molecular Medicine
DOI: 10.15252/emmm.20191111511 / 2019
Nature Protocols
Breckwoldt, K. and Breni{\`e}re-Letuffe, D. and Mannhardt, I. and Schulze, T. and Ulmer, B. and Werner, T. and Benzin, A. and Klampe, B. and Reinsch, M.C. and Laufer, S. and Shibamiya, A. and Prondzynski, M. and Mearini, G. and Schade, D. and Fuchs, S. and Neuber, C. and Kr{\"a}mer, E. and Saleem, U. and Schulze, M.L. and Rodriguez, M.L. and Eschenhagen, T. and Hansen, A.
DOI: 10.1038/s41596-019-0228-5Pflugers Archiv European Journal of Physiology
Prondzynski, M. and Mearini, G. and Carrier, L.
DOI: 10.1007/s00424-018-2173-5Journal of Molecular and Cellular Cardiology
Morhenn, K. and Quentin, T. and Wichmann, H. and Steinmetz, M. and Prondzynski, M. and S{\"o}hren, K.-D. and Christ, T. and Geertz, B. and Schr{\"o}der, S. and Sch{\"o}ndube, F.A. and Hasenfuss, G. and Schlossarek, S. and Zimmermann, W.H. and Carrier, L. and Eschenhagen, T. and Cardinaux, J.-R. and Lutz, S. and Oetjen, E.
DOI: 10.1016/j.yjmcc.2018.12.001Circulation: Arrhythmia and Electrophysiology
Lemoine, M.D. and Krause, T. and Koivum{\"a}ki, J.T. and Prondzynski, M. and Schulze, M.L. and Girdauskas, E. and Willems, S. and Hansen, A. and Eschenhagen, T. and Christ, T.
DOI: 10.1161/CIRCEP.117.006035European Heart Journal
Mosqueira, D. and Mannhardt, I. and Bhagwan, J.R. and Lis-Slimak, K. and Katili, P. and Scott, E. and Hassan, M. and Prondzynski, M. and Harmer, S.C. and Tinker, A. and Smith, J.G.W. and Carrier, L. and Williams, P.M. and Gaffney, D. and Eschenhagen, T. and Hansen, A. and Denning, C.
DOI: 10.1093/eurheartj/ehy249Circulation: Heart Failure
Singh, S.R. and Zech, A.T.L. and Geertz, B. and Reischmann-D{\"u}sener, S. and Osinska, H. and Prondzynski, M. and Kr{\"a}mer, E. and Meng, Q. and Redwood, C. and Van Der Velden, J. and Robbins, J. and Schlossarek, S. and Carrier, L.
DOI: 10.1161/CIRCHEARTFAILURE.117.004140Scientific Reports
Lemoine, M.D. and Mannhardt, I. and Breckwoldt, K. and Prondzynski, M. and Flenner, F. and Ulmer, B. and Hirt, M.N. and Neuber, C. and Horv{\'a}th, A. and Kloth, B. and Reichenspurner, H. and Willems, S. and Hansen, A. and Eschenhagen, T. and Christ, T.
DOI: 10.1038/s41598-017-05600-wToxicological Sciences
Mannhardt, I. and Eder, A. and Dumotier, B. and Prondzynski, M. and Kr-amer, E. and Traebert, M. and Flenner, F. and Stathopoulou, K. and Lemoine, M.D. and Carrier, L. and Christ, T. and Eschenhagen, T. and Hansen, A.
DOI: 10.1093/toxsci/kfx081Nature Protocols
Breckwoldt, K. and Letuffe-Breni{\`e}re, D. and Mannhardt, I. and Schulze, T. and Ulmer, B. and Werner, T. and Benzin, A. and Klampe, B. and Reinsch, M.C. and Laufer, S. and Shibamiya, A. and Prondzynski, M. and Mearini, G. and Schade, D. and Fuchs, S. and Neuber, C. and Kr{\"a}mer, E. and Saleem, U. and Schulze, M.L. and Rodriguez, M.L. and Eschenhagen, T. and Hansen, A.
DOI: 10.1038/nprot.2017.033Molecular Therapy - Nucleic Acids
Prondzynski, M. and Kr{\"a}mer, E. and Laufer, S.D. and Shibamiya, A. and Pless, O. and Flenner, F. and M{\"u}ller, O.J. and M{\"u}nch, J. and Redwood, C. and Hansen, A. and Patten, M. and Eschenhagen, T. and Mearini, G. and Carrier, L.
DOI: 10.1016/j.omtn.2017.05.008Journal of Biological Chemistry
Theis, T. and Mishra, B. and Von Der Ohe, M. and Loers, G. and Prondzynski, M. and Pless, O. and Blackshear, P.J. and Schachner, M. and Kleene, R.
DOI: 10.1074/jbc.M112.444034Hypertrophic cardiomyopathy (HCM) is a complex and highly heterogeneous disease that can result in asymmetric cardiac hypertrophy, myofibrillar disarray, and serious arrhythmogenesis that can cause sudden cardiac arrest (SCA). In fact, HCM is the leading cause of SCA in the youth, and elite athletes. HCM is a genetic disorder inherited in an autosomal dominant pattern with a frequency of about ~1/500. To date over 1,400 HCM-associated variants have been identified > 12 genes encoding sarcomeric proteins. Variants in genes encoding thick filament proteins cardiac myosin ß heavy chain (MYH7) and myosin binding protein C (MYBPC3) account for ~40% of HCM cases. On the other hand, genes encoding for thin filament proteins troponin I (TNNI3), troponin C (TNNC1), and troponin T (TNNT2) account for ~30% of HCM cases. These are of particular interest, however, because while the degree of hypertrophy could be minimal, the arrhythmogenicity could be serious enough to result in SCA. Thus, clinical screening of patients using echocardiography will likely result in a false negative diagnosis, yet they remain at high risk for SCA and is the focus of this proposal.
The overall objective of this proposal is to understand better how thin filament variants associated with HCM can impact cardiac contraction and arrhythmogenesis and strategies for effective therapies. The focus will on using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) harboring variants in the genes encoding TNNC1, TNNI3, and TNNT2. We will use a suite of complementary approaches to delve deeper into the mechanisms of pathogenicity.
Over the last few years, exciting progress has been made in certain aspects of HCM and has resulted in the very recent FDA approval (April 2022) of the first and only drug for its treatment, mavacamten, a myosin ATPase inhibitor. A very recent focus has been on the myosin state during diastole, including a super-relaxed (SRX or closed) and a disordered relaxed (DRX or open) state. In the healthy heart, 40–50% of the myosin heads are in the SRX state with negligible ATP consumption, whereas in HCM there is a shift in this ratio, with only 15–20% of the myosin heads being in the SRX state. The increased myosin in the DRX state with HCM increases ATP consumption and the myosin heads are more primed to interact with actin. This cause excess myosin–actin cross-bridges during both systole and diastole leading to a hypercontractile state and diastolic dysfunction. Targeting the myosin ATPase with mavacamten has been shown to increase myosin SRX conformations by acting on multiple stages of the myosin chemomechanical cycle.
However, as promising as this seems, there is now growing evidence that mavacamten is not as effective in treating HCM cases resulting from troponin variants, despite the phenotype for this subclass also exhibiting a hypercontractile state and impaired relaxation. Potential mechanisms for thin filament associated HCM phenotype include alterations of the tropomyosin positioning on actin and increased myofilament Ca2+ sensitivity.
Thus, the aim of this proposal is to study the mechanisms of the HCM-related pathogenicity of TNNC1, TNNI3, and TNNT2 variants in terms of the contractile and electrophysiological state using state of the art models including reconstituted thin recombinant proteins, hiPSC-CMs organized in both 2D (monolayers) and 3D (cardioids) tissue structures.
SK channels (SK1, SK2, and SK3) are Ca-activated K channels encoded by three genes, KCNN1, KCNN2, and KCNN3. While the tissue specificity and function of these ion channels remain controversial, there is a strong Genome-Wide Association Studies (GWAS) associated correlation, for example, with SK3 ion channel variants (e.g., 1q21 rs13376333 (RS)) and atrial fibrillation (AF). While GWAS play an important role in hypothesis generation, the data are only correlative in nature and not proof of causality. In a series of elegant studies, our collaborator L Hove Madsen used patient-derived native atrial appendage cells to study the electrophysiological properties, live cell imaging, and protein distribution that are distinct in AF patients. Although sophisticated, these studies do have shortcomings common to all native human heart tissue studies including co-morbidities, chronic drug treatment, and lack of suitable controls.
We used CRISPR Cas9 to create the AF-associated RS variant along with their isogenic controls (WT) in hiPSCs. This proposal includes some exciting preliminary data from these variant harboring hiPSC-derived atrial cardiomyocytes (hiPSC-aCMs). The same genome editing strategies /constructs will be used to create these in additional hiPSC lines that were generated from both male and female healthy donors. We also have adopted a hiPSC-CM maturation protocol which significantly enhances mitochondrial density, metabolic capacity, the formation of T-tubules and dyads, and myofibrillar alignment.
Arrhythmogenicity will be tested on 3D bioprinted atrial tissue (3DBAT) over a range of stimulation frequencies (1-4 Hz), ± ß adrenergic agonists, and rotor-inducing stimulation protocols. Using high-speed (1000 fps) optical mapping (OM), action potential duration (APD), Ca transient duration, and conduction velocity and dispersion will be measured. The potential for early afterdepolarizations, re-entry loops, and rotors will be determined. Once the OM is complete, Cell Painting will be used to examine cell nuclei, sarcomere alignment, collagen formation, and the cell-to-cell arrangement. Our aims are to use:
1. 3DBAT made of hiPSC-aCMs (± RS) and a bioink for the ECM, to test the hypothesis that APD prolongation will be observed in RS and an increased potential for arrhythmogenicity.
2. 3DBAT made of hiPSC-derived atrial cells and fibroblasts. Both cell types will be made from the same hiPSC line (± RS) at a ratio of 4:1 to test the hypothesis that co-bioprinting with fibroblasts will mature the hiPSC-aCMs based on their proteomic and morphological profile.
3. same 3DBAT as in aim 2 except TGFß will be used to activate fibroblasts to collagen-producing myofibroblasts, to test the hypothesis that atrial fibrosis will change the biomechanical and electrical properties of the atrial tissue increasing the arrhythmogenicity.
4. bioreactor based 3D differentiation of hiPSCs to atrial cardiomyocytes. While the other three aims are not predicated on the success of this aim, achieving this will be transformative for the field by generating hundreds of millions of hiPSCaCM all exposed to identical conditions.
This approach to understanding the mechanisms of familial AF exploits a cutting-edge platform of hiPSC-derived atrial tissue and an impressive array of phenotyping tools to understand the mechanisms of atrial arrhythmogenicity. The data generated should offer deeper insight into potential personalized therapeutic AF interventions.
Congenital heart disease (CHD) is the most common organ malformation in newborns. A genetic etiology can be linked to about 50% of CHD. Developing therapeutic interventions based on this genetic information requires understanding how gene mutations cause CHD. Experiments in model organisms have provided invaluable insights, but human heart development has unique features that are not replicated in animal models, particularly commonly used models such as mice and zebrafish. For example, cardiac gene expression differs in humans, making animal models unable to mimic certain aspects of human development and disease. Clearly a model of human heart development would be invaluable for further mechanistic studies and for the development of therapeutic interventions based on our growing understanding of genetic causes and pathogenic mechanisms. We developed a protocol to reproducibly generate cardiac organoids (COs) from human induced pluripotent stem cells (iPSCs) in 15 days. The protocol uses a stirred bioreactor, which produces controlled hemodynamic forces and carefully regulates the cell environment. Our bioreactor-derived COs (bCOs) undergo self-patterning and morphogenesis, forming hollow spheres several fold larger than previously described COs. The walls, primarily composed of iPSC-CMs, envelop central cavities reminiscent of cardiac chambers. We found that COs also contain endothelial cells and fibroblasts, and mutant COs lacking a cardiac specific RNA binding protein exhibited morphological defects. Based on these observations, we propose to establish bCOs as a novel platform for investigation of CHDs in the human context.
Co-Primary Investigator. Using hiPSC-derived atrial tissue to understand better the role of SK ion channel variants in atrial fibrillation. Funding Source: CIHR
Co-Primary Investigator. Mechanisms by which thin filament variants induce hypertrophic cardiomyopathy. Funding Source: CIHR
Co-Investigator. Modeling human heart morphogenesis with bioreactor-derived cardiac organoids. Funding Source: Additional Ventures, Single Ventricle Research Foundation
Co-Investigator. Tissue Chips for Precision Treatment of Catecholaminergic Polymorphic Ventricular Tachycardia. Funding Source: National Center for Advancing Translational Sciences
2024 - Merit Abstract award, International Society for Stem Cell Research (ISSCR). Poster presentation of the project: “Suspension culture-derived organoid models of cardiac development”
2021 - Oral presentation award, Dr. M. Judah Folkman Research Day, Boston Children's Hospital, “Modeling of a novel Filamin-C mutation in hiPSC-derived cardiomyocytes resemble restrictive cardiomyopathy phenotypes”
2019 - Wilhelm P. Winterstein-Preis, German Heart Foundation, “Disease modeling reveals causative role for an Alpha-actinin 2 mutation and a diltiazem-reversible long QT phenotype in hypertrophic cardiomyopathy – an example of personalized medicine”
2018 - Young investigator award, International Society for Heart Research (ISHR), “CRISPR/Cas9 genome editing repairs a novel ACTN2 mutation and prevents the disease phenotype in human iPSC-derived cardiomyocytes and engineered heart tissue”
2017 - Prize for Doctoral Thesis, Cardiovascular Research Center (CVRC), “Modeling of hypertrophic cardiomyopathy and assessment of gene therapy in human iPSC-derived cardiomyocytes”
2015 - Poster prize, German Center for Cardiovascular Research. “2D culture of hiPSC-derived cardiomyocytes to evaluate molecular therapy and cell size”
At BC Children’s, we are making discoveries that save lives and transform health care for children in our province and around the world. Our research portfolio includes basic, clinical, population, and public health research.
EXPLORE OUR RESEARCH
Sign up for compelling stories about innovative science, the doctors and researchers who turn ideas into discoveries and treatments, and the kids and families whose lives are changed.
BC Children's Hospital Research Institute operates on the ancestral and unceded territory of the Coast Salish peoples — xʷməθkʷəy̓əm (Musqueam), Sḵwx̱wú7mesh (Squamish), and Səl̓ílwətaʔ/Selilwitulh (Tsleil-Waututh) Nations. Further, this acknowledgement, gratitude, and respect extends to all of the First Nations communities on whose territories the Research Institute builds relationships and operates in British Columbia.
© 2026 BC Children’s Hospital Research Institute. All rights reserved.
Crafted with by Forge and Smith
